NAT10 Suppresses RNA Sensing Induced IFN-β Transactivation to Promote Viral Infection via Interfering with IRF3 Activities
Park, Y.; He, J.; Eleya, S.; Wu, Z.; Fiches, G. N.; Zhou, D.; Watters, E. G.; He, Z. M.; Shanaka, K. A.; Lepcha, T. T.; Liu, Y.; Santoso, N. G.; Zhu, J.
Show abstract
Cells can sense invading viruses and trigger type I interferons (IFN-/{beta}) to evoke antiviral innate immune response. Induction of IFNs needs to be fine-tuned to achieve the antiviral consequence while avoiding severe disruption of host cell homeostasis. Here, we reported that NAT10, the acetyltransferase of histone and N4-acetylcytidine (ac4C) RNA modification, promotes infection of RNA viruses via regulation of type I IFN signaling. Depletion of NAT10 increased the expression of IFN-{beta} and interferon-stimulated genes (ISGs) upon stimulation of type I IFN antiviral signaling, while it impaired viral replication. NAT10 dynamically associated with the IFN-{beta} promotor and negatively regulated IRF3 through modulation of long non-coding RNAs (lncRNAs) that inhibit IRFs. Consistently, the small molecule inhibitor of NAT10, Remodelin, increased IFN-{beta} expression while inhibiting viral infections. Overall, our findings indicated that NAT10 is a negative regulator of type I IFN signaling, suggesting its potential as a target of antiviral treatment.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.